The objective of the experiments proposed is to provide basic biochemical information regarding the rate of deoxyhemoglobin S polymerization and molecular detail regarding the specific interaction between deoxyhemoglobin S molecules. Transverse water proton relaxation rates will be used to measure the delay time and determine the rate of deoxyhemoglobin S polymerization and its reversal. Polymerization will be initiated by rapidly mixing hemoglobin S and sodium dithionite or by jumping the temperature of deoxyhemoglobin S samples to 37 degrees. We will investigate how the non-gelling hemoglobins F and A2 inhibit deoxyhemoglobin S polymerization. Since a certain percentage of individuals with sickle cell disease have no clinical problems we will investigate whether the rate of polymerization is affected by slight variation in the 2,3 diphosphoglycerate concentration and the percentage of deoxygenation. Furthermore, the rate of polymerization in intact erythrocytes will be measured to examine what role the erythrocyte membrane may have in the rate of Polymerization. We propose to use specifically carbamylated hemoglobin S to detect conformation changes near the amino terminus of both the alpha ahd beta chains. Experiments are also proposed at other NMR frequencies and mole fractions of deuterium oxide to investigate in detail the relaxation mechanism that gives rise to the shortened T2 measurements during polymerization. By more detailed information on how the physiological environment effects the rate of deoxyhemoglobin S polymerization, it may be possible to slow the rate of polymerization sufficiently so that cell sickling does not occur before the erythrocyte traverses the circulation and becomes reoxygenated.